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In their systematic review, Navarese and colleagues (1) conclude that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce all-cause mortality (odds ratio [OR], 0.45 [95% CI, 0.23 to 0.86]) and rates of myocardial infarction and have a favorable, yet not statistically significant, effect on cardiovascular mortality (OR, 0.50 [CI, 0.23 to 1.10]) and unstable angina. They claim robustness of their findings based on similar results from several sensitivity analyses.

We question these conclusions in light of a reanalysis of the all-cause mortality data. The authors excluded 0-total-event trials and used an inverse variance–weighted fixed-effects model for pooling rare events. This model relies on large sample theory and has shown poor performance with rare events in simulation studies (2). We repeated the analysis including all trials and used a Mantel–Haenszel (MH) weighted fixed-effects model and treatment-group continuity correction (most trials had no outcome events for the primary outcomes), as previously described for rosiglitazone studies (3). This analysis found that the effect estimate for all-cause mortality is, indeed, sensitive to the exclusion of 0-total-event trials (OR, 0.62 [CI, 0.37 to 1.04]).